(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate → 2-[4-(5-Methyl-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-ylmethyl]-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

HRID 989773Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 989773
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:27][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]4)(=O)=O)=CC=1.[CH3:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][CH:33]=[C:32]2[C:38]1[CH2:39][CH2:40][NH:41][CH2:42][CH:43]=1>CS(C)=O>[CH3:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][CH:33]=[C:32]2[C:38]1[CH2:39][CH2:40][N:41]([CH2:12][CH:13]2[O:27][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]4)[CH2:42][CH:43]=1

Komponenten

4

Edukt 2

HCID 11280604(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonateHCID 181803115-Methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

Produkt 1

HCID 101807732-[4-(5-Methyl-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-ylmethyl]-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.55 g, 1.4 mmole) and 5-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.80 g, 3.8 mmole) were combined in 10 mL of DMSO. The mixture was heated at 70-80 ° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL each of ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was removed, washed with saturated brine, dried over magnesium sulfate, filtered and concentrated to dryness under vacuum. The residue was column chromatographed on silica gel using 0-2% methanol/chloroform as eluant. The product-containing fractions were concentrated in vacuum and the residue recrystallized from isopropanol with the addition of fumaric acid to give 0.32 g of the (S)-enantiomer of the title compound as a yellow solid monofumarate, three-quarter hydrate (m.p. 150-155° C.).

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between 400 mL each of ethyl acetate and saturated aqueous sodium bicarbonate
  3. customThe organic phase was removed
  4. washwashed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under vacuum
  8. customchromatographed on silica gel using 0-2% methanol/chloroform as eluant
  9. concentrationThe product-containing fractions were concentrated in vacuum
  10. customthe residue recrystallized from isopropanol with the addition of fumaric acid

Quellen und Nachweise

ORD-Eintrag
ord-ed2e58ee555d4ebf9449111881dcab2f
Quelldatensatz
uspto-grants-2002_10
Patentnummer
US06458802B1

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